Glaucoma is a group of diseases that slowly and progressively damage the optic nerve head leading to impaired vision and eventually, blindness. It is the third leading cause of blindness, affecting nearly 3 million Americans, age 40 and over, and 67 million people worldwide. In most cases, this progressive vision loss is associated with an increase in intraocular pressure. Elevated pressure increases the mechanical stress in the sclera and the support structures surrounding the optic nerve head including the lamina cribrosa. It has been hypothesized that the astrocytes, lamina cribrosa cells, microglia, and fibroblasts, cells which normally maintain the connective tissue matrix, respond by producing chemical factors that damage and eventually kill axons in the optic nerve head. Other mechanisms by which such pressure may lead to optic nerve head damage include sudden failure of the connective tissue support structures and acute or chronic ischemia resulting from an adverse blood pressure gradient. In an effort to understand the degenerative processes characteristic of glaucoma, we propose to develop innovative experimental models of the effects of mechanical loading and ischemia on the connective tissue cells and support cells in the lamina cribrosa. Specifically we will investigate the long-term effects of optic nerve head displacement using an experimental model that reproduces the complex cellular level deformations developed in vivo. In addition we will combine this mechanical model of the lamina cribrosa with simulated ischemia in order to better understand the interaction between these two damage mechanisms. The data generated by this research will provide a basis for future efforts aimed at understanding the effects of drug treatments on glaucomatous degeneration and the interactions between the support cells and the axons in the optic nerve head.